To determine the alternate pathways of heme and bilirubin metabolism in: 1. Congenital deficiency of hepatic bilirubin conjugation (Gunn rat). 2. Phototherapy of the Gunn rat and of jaundiced newborn infants. 3. Unstable hemoglobinopathies with Heinz-body formation. 4. Drug-induced porphyria in rats due to allyl-isopropyl-acetamide. In each case, will isolate, and identify by mass spectroscopy, labeled metabolitesexcreted after administration of C14-bilirubin or hemoglobin. Will also determine by classical enzymological methods, the subcellular fractions and enzymes involved in the formation of these bilirubin and heme metabolites by the liver. To study the effects of phototherapy on: 1. Hepatic excretion bile salts, BSP, and lipid- soluble drugs in both: a. Humans with alcoholic cirrhoris or primary biliary cirrhosis. b. Rats with cholestasis due to icterogenin or alpha-naphthyl-isothiocyanate. 2. Hepatic drug metabolizing enzyme activity and cytochrome P450 content. 3. Excretion of unconjugated bilirubin in bile and mechanism of this effect. 4. Cytotoxicity and protein-binding of bilirubin and its in vivo photoderivatives. To investigate the mechanism of pigment gallstones: 1. Identify the insoluble black pigment, the major component of pigment stones. 2. Develop methods for large-scale isolation and simple, accurate, quantitative determination of bilirubin conjugates in bile. 3. Determine in model systems the effects of pH, micellar components, proteins, calcium and bilirubin conjugates on the solubility of unconjugated bilirubin. 4. Study rates of hydrolysis of conjugated bilirubin in the bile of subjects with and without pgiment stones, and identfy the enzyme(s) responsible.